Predictive liquid markers for cancer immunotherapy

Abstract

The present disclosure relates generally to methods and compositions for cancer immunotherapy, and more specifically, liquid markers for predicting effectiveness of cancer therapies. The disclosure features compositions and methods that are useful for predicting the efficacy of cancer treatment (e.g., a checkpoint inhibitor immunotherapy) and, in some embodiments, administering the cancer treatment such as immunotherapy.

1 . A method for predicting or monitoring effectiveness of cancer immunotherapy, comprising:
 providing a bodily fluid sample from a subject, wherein the bodily fluid sample comprises extracellular vesicles;   analyzing the sample using an integrated magnetic-electrochemical sensing system; and   determining an amount of one or more biomarkers that are associated with the extracellular vesicles, wherein the biomarkers are selected from: MLH1, MSH2, MSH6, PMS2, Perforin, Granzymes, IL-2, IL-6, IL-12, TCF7, and Lin28, and optionally one or more of PD-L1, CD47, and PD-1.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the bodily fluid sample is plasma and/or urine. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the determining step comprises using a SingleMarkerScore method, a CategoryScore method, a RegressionScore method, a DecisionTreeScore method, or a NeuralNetworkScore method. 
     
     
         6 . The method of  claim 1 , wherein the cancer immunotherapy is PD-1/PD-L1, CTLA4, and/or CD47 blockade. 
     
     
         7 . The method of  claim 1 , wherein the cancer is one or more of: bladder, gastric cancer, lung cancer, colon cancer, prostate cancer, renal cell carcinoma, head and neck cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), glioblastoma, medulloblastoma, oral squamous cell carcinoma, breast cancer, ovarian cancer, cervical cancer, testicular germ cell tumor, and Wilms tumor. 
     
     
         8 . A method for diagnosing or prognosing cancer, comprising:
 providing a bodily fluid sample from a subject, wherein the bodily fluid sample comprises extracellular vesicles;   analyzing the sample using an integrated magnetic-electrochemical sensing system; and   determining an elevated amount of a biomarkers that are associated with the extracellular vesicles, in comparison with a control, wherein the biomarker is Lin28 and optionally one or more of PD-L1, CD47, and PD-1.   
     
     
         9 . The method of  claim 8 , wherein the bodily fluid sample is plasma and/or urine. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 8 , wherein the determining step comprises using a SingleMarkerScore method, a CategoryScore method, a RegressionScore method, a DecisionTreeScore method, or a NeuralNetworkScore method. 
     
     
         12 . The method of  claim 8 , wherein the cancer is one or more of: bladder, gastric cancer, lung cancer, colon cancer, prostate cancer, renal cell carcinoma, head and neck cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), glioblastoma, medulloblastoma, oral squamous cell carcinoma, breast cancer, ovarian cancer, cervical cancer, testicular germ cell tumor, and Wilms tumor. 
     
     
         13 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, and Lin28. 
     
     
         14 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, and IL-12. 
     
     
         15 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, and TCF7. 
     
     
         16 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, perforin, and granzymes. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, IL-12 and TCF7. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the biomarkers are PD-L1, CD47, TCF7, and IL-12. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the biomarkers are PD-L1, Perforin, Granzymes, IL-12, and TCF7. 
     
     
         25 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, Perforin, Granzymes, IL-12, and TCF7. 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, PD-L1, CD47, Perforin, Granzymes, IL-12, and TCF7. 
     
     
         29 . The method of  claim 1 , wherein the biomarkers are PD-L1, CD47, Perforin, Granzymes, IL-12, TCF7, and Lin28. 
     
     
         30 . The method of  claim 1 , wherein the biomarkers are MLH1, MSH2, MSH6, PMS2, PD-L1, CD47, PD-1, Perforin, Granzymes, IL-2, IL-6, IL-12, TCF7, and Lin28.